A tissue known as stratum corneum exists on the outermost layer of the skin, which has a moisturizing function for retaining moisture as well as a barrier function for protecting the skin against external stimulation. The stratum corneum consists of keratinocytes, natural moisturizing factors and intercellular lipids, among which ceramides account for approximately one-half of the total intercellular lipids and play a crucial role for these functions. For example, a common characteristic of atopic dermatitis and senile xerosis is a significant deterioration of moisturizing ability, which is known to mainly result from decreased ceramide levels due to lipid metabolic enzyme abnormalities. Ceramides have also been shown to enhance barrier function, provide whitening effect and inhibit melanogenesis. Ceramides can be externally supplied.
J Invest Dermatol. 96:523-526, 1991 (Non-patent document 1) and Arch Dermatol Res. 283:219-223, 1991 (Non-patent document 2) disclose “decreased ceramide levels in atopic dermatitis and senile xerosis”; J Dermatol Sci. 1:79-83, 1990 (Non-patent document 3) and Acta Derm Venereol. 74:337-340, 1994 (Non-patent document 4) disclose “decreased ceramide levels and lipid metabolic enzyme abnormalities”; Contact Dermatitis. 45:280-285, 2001 (Non-patent document 5) and J Eur Acad Dermatol Venereol. 16:587-594, 2002 (Non-patent document 6) disclose “restoration of barrier function by ceramides”; and Cell Signal 14:779-785, 2002 (Non-patent document 7) discloses “inhibition of melanogenesis by ceramides.”
Recently, ceramides have attracted great attention for use in medicines for skin diseases associated with dry sensitive skin or in cosmetics or health and/or cosmeceutical foods. In fact, a number of products such as cosmetics and food or supplements containing ceramides have already been commercialized, and the market for ceramide materials is continuing to grow.
Ceramide materials of animal origin such as cow were conventionally used, but are currently replaced by those of plant origin such as rice, wheat, soybean and potato because of problems of infections. A recent basic study (J. Clin. Invest. 112:1372-1382, 2003 (Non-patent document 8)) showed the importance of the structures of ceramides in the moisturizing and barrier functions of the skin, which raised questions about whether plant ceramides structurally different from human ceramides are highly functional lipids. Moreover, ceramides are present in animals and plants in minute amounts and are difficult to extract and purify, thus incurring low productivity and high cost, and therefore, it is highly desirable to develop a new production technique capable of overcoming these problems.
It is known that, in the synthetic/metabolic pathway for sphingolipids, reactions downstream of dihydrosphingosine (DHS) biosynthesis widely differ between higher animal cells (including human cells) and yeast cells, as shown in FIG. 1. Each enzyme protein involved in various steps in the synthetic/metabolic pathway for sphingolipids and the gene encoding the protein have been known to some degree (Biochemistry. 41:15105-15114, 2002 (Non-patent document 9); J Biol Chem. 277:25512-25518, 2002 (Non-patent document 10); Yeast 9: 267-277, 1993 (Non-patent document 11); J Biol Chem 272:29704-29710, 1997 (Non-patent document 12); J Biol Chem 275:31369-31378, 2000 (Non-patent document 13); J Biol Chem 275:39793-39798, 2000 (Non-patent document 14)).
Non-patent document 1: J Invest Dermatol. 96:523-526, 1991
Non-patent document 2: Arch Dermatol Res. 283:219-223, 1991
Non-patent document 3: J Dermatol Sci. 1:79-83, 1990
Non-patent document 4: Acta Derm Venereol. 74:337-340, 1994
Non-patent document 5: Contact Dermatitis. 45:280-285, 2001
Non-patent document 6: J Eur Acad Dermatol Venereol. 16:587-594, 2002
Non-patent document 7: Cell Signal 14:779-785, 2002
Non-patent document 8: J. Clin. Invest. 112:1372-1382, 2003
Non-patent document 9: Biochemistry. 41:15105-15114, 2002
Non-patent document 10: J Biol Chem. 277:25512-25518, 2002
Non-patent document 11: Yeast 9: 267-277, 1993
Non-patent document 12: J Biol Chem 272:29704-29710, 1997
Non-patent document 13: J Biol Chem 275:31369-31378, 2000
Non-patent document 14: J Biol Chem 275:39793-39798, 2000